Comparison of Mitotic Count and Ki-67 Index in Grading Gastroenteropancreatic Neuroendocrine Tumors and Their Association with Metastases

<b>Background</b>: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are graded per the World Health Organization (WHO) using mitotic count and the Ki-67 index. There is an ongoing debate regarding the concordance between these parameters and their ability to predict metastatic disease. <b>Objective</b>: The objective is to assess concordance between the mitotic count and the Ki-67 index in grading GEP-NETs and to determine which parameter more accurately relates to metastatic disease and local tumor behavior. <b>Methods</b>: We conducted a single-center retrospective cohort study of adults with GEP-NETs managed between January 2006 and February 2024. Tumors were staged according to the TNM system. Grading followed WHO criteria using mitotic count and the Ki-67 index; when discordant, the higher grade was assigned. <b>Results</b>: Concordance between mitotic count- and Ki-67-based grading was 76.5% (78/102) with Cohen’s κ = 0.36, indicating fair-to-moderate agreement. More tumors were classified as G1 by mitotic count (86.3%) than by the Ki-67 index (68.6%). Neither mitotic count nor the Ki-67 index (numerical values or grades) showed a significant association with metastatic disease (all <i>p</i> > 0.05). Mitotic count (as a numerical continuous values) correlated with tumor invasion (T1 vs. T3, <i>p</i> = 0.035; T1 vs. T4, <i>p</i> = 0.036), whereas the Ki-67 index did not (<i>p</i> = 0.11). Tumor size was the strongest predictor of metastases (lymph-node <i>p</i> = 0.028; distant <i>p</i> < 0.001; any <i>p</i> < 0.001). <b>Conclusions</b>: Mitotic count and the Ki-67 index show only 76.5% concordance. Neither marker predicted metastatic disease in this cohort, while tumor size was the most robust predictor. These findings support giving greater weight to tumor size within prognostic algorithms while recognizing the limitations of proliferation-based grading for predicting metastasis.